Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

Jinkai Wan; Shenghui Xing; Longfei Ding; Yongheng Wang; Chenjian Gu; Yanling Wu; Bowen Rong; Cheng Li; Siqing Wang; Kun Chen; Chenxi He; Dandan Zhu; Songhua Yuan; Chengli Qiu; Chen Zhao; Lei Nie; Zhangzhao Gao; Jingyu Jiao; Xiaoyan Zhang; Xiangxi Wang; Tianlei Ying; Haibin Wang; Youhua Xie; Yanan Lu; Jianqing Xu; Fei Lan

doi:10.1016/j.celrep.2020.107918

Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

Cell Rep. 2020 Jul 21;32(3):107918. doi: 10.1016/j.celrep.2020.107918. Epub 2020 Jul 3.

Authors

Jinkai Wan¹, Shenghui Xing¹, Longfei Ding², Yongheng Wang³, Chenjian Gu⁴, Yanling Wu⁴, Bowen Rong¹, Cheng Li⁴, Siqing Wang¹, Kun Chen¹, Chenxi He¹, Dandan Zhu⁵, Songhua Yuan², Chengli Qiu², Chen Zhao², Lei Nie⁶, Zhangzhao Gao⁶, Jingyu Jiao⁶, Xiaoyan Zhang⁷, Xiangxi Wang⁵, Tianlei Ying⁴, Haibin Wang⁶, Youhua Xie⁸, Yanan Lu⁹, Jianqing Xu¹⁰, Fei Lan¹¹

Affiliations

¹ Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
³ Active Motif China, Inc., Shanghai 201315, China.
⁴ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁵ National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
⁶ Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou City, Zhejiang Province 318000, China.
⁷ Shanghai Public Health Clinical Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
⁸ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: yhxie@fudan.edu.cn.
⁹ Active Motif China, Inc., Shanghai 201315, China. Electronic address: ylu@activemotif.com.
¹⁰ Shanghai Public Health Clinical Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China. Electronic address: xujianqing@shphc.org.cn.
¹¹ Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: fei_lan@fudan.edu.cn.

Abstract

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC₅₀ below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC₅₀ within 10 nM, and the best one, 414-1, with IC₅₀ of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.

Keywords: COVID-19; RBD; SARS-CoV-2; coronavirus; cross-neutralizing antibody; epitope; human antibodies; infection; neutralizing antibodies; spike protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / therapeutic use
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
B-Lymphocytes / immunology
Betacoronavirus / immunology*
COVID-19
Coronavirus Infections / therapy
Epitope Mapping
Epitopes / immunology
Humans
Immunologic Memory / immunology
Neutralization Tests
Pandemics
Pneumonia, Viral / therapy
Protein Domains / immunology
Receptors, Virus / immunology*
SARS-CoV-2
Spike Glycoprotein, Coronavirus / immunology*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Epitopes
Receptors, Virus
Spike Glycoprotein, Coronavirus